TY - JOUR N2 - Animals as a source of organs and tissues for xenotransplantation could become a backup solution for the growing shortage of human donors. The presence of human xenoreactive anti- bodies directed against Galα1,3Gal antigens on the cell surface of a pig donor triggers the activa- tion of the complement leading to a hyperacute reaction. The development of genetic engineer- ing techniques has enabled the modification of genomes by knocking in and/or knocking out genes. In this paper, we report the generation of modified pigs with ZFN mediated disruption of the GGTA1 gene encoding the enzyme responsible for synthesis of Galα1,3Gal antigens. ZFN plasmids designed to target the exon 9 region of the pig GGTA1 gene encoding the catalytic domain were injected into the pronuclei of fertilized egg cells. Among 107 piglets of the F0 gene- ration analyzed, one female with 9-nt deletion in exon 9 of the GGTA1 gene was found. 13 of 33 piglets of the F1 generation represented the +/- GGTA1 genotype and 2 of 13 F2 piglets repre- sented the -/- GGTA1 genotype. No changes in the animals’ behavior, phenotype or karyotype were observed. Analysis confirmed heredity of the trait in all animals. A complex functional analysis of the modified animals, including flow cytometry, human serum cytotoxicity test and immunohistochemical detection, was performed to estimate the phenotype effect of genetic modification and this indicated an efficient GGTA1 knock-out in modified pigs. L1 - http://www.journals.pan.pl/Content/109603/PDF/13.pdf L2 - http://www.journals.pan.pl/Content/109603 PY - 2019 IS - No 1 EP - 100 DO - 10.24425/pjvs.2018.125611 KW - Galα1 KW - 3Gal epitopes KW - pigs KW - xenotransplantation KW - genome edition KW - ZFNs KW - functional characteristics A1 - Lipiński, D. A1 - Nowak-Terpiłowska, A. A1 - Hryhorowicz, M. A1 - Jura, J. A1 - Korcz, A. A1 - Słomski, R. A1 - Juzwa, W. A1 - Mazurkiewicz, N. A1 - Smorąg, Z. A1 - Zeyland, J. PB - Polish Academy of Sciences Committee of Veterinary Sciences PB - University of Warmia and Mazury in Olsztyn VL - vol.22 DA - 2019.04.04 T1 - Production of ZFN-mediated GGTA1 knock-out pigs by microinjection of gene constructs into pronuclei of zygotes SP - 91 UR - http://www.journals.pan.pl/dlibra/publication/edition/109603 T2 - Polish Journal of Veterinary Sciences ER -